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Nature Reviews. Neuroscience Sep 2021Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces... (Review)
Review
Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. These end organ structures comprise a range of non-neuronal cell types, which may themselves actively contribute to the transformation of tactile forces into neural impulses within the LTMR afferents. Although the mechanism and the site of transduction across end organs remain unclear, PIEZO2 has emerged as the principal mechanosensitive channel involved in light touch of the skin. Here we review the physiological properties of LTMR subtypes and discuss how features of their cutaneous end organ complexes shape subtype-specific tuning.
Topics: Animals; Humans; Mechanoreceptors; Skin; Touch
PubMed: 34312536
DOI: 10.1038/s41583-021-00489-x -
Cell Aug 2023The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology...
The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.
Topics: Ganglia, Spinal; Mechanoreceptors; Colon; Neurons; Skin
PubMed: 37541195
DOI: 10.1016/j.cell.2023.07.007 -
Cell Research Jan 2016Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based...
Sensory neurons are distinguished by distinct signaling networks and receptive characteristics. Thus, sensory neuron types can be defined by linking transcriptome-based neuron typing with the sensory phenotypes. Here we classify somatosensory neurons of the mouse dorsal root ganglion (DRG) by high-coverage single-cell RNA-sequencing (10 950 ± 1 218 genes per neuron) and neuron size-based hierarchical clustering. Moreover, single DRG neurons responding to cutaneous stimuli are recorded using an in vivo whole-cell patch clamp technique and classified by neuron-type genetic markers. Small diameter DRG neurons are classified into one type of low-threshold mechanoreceptor and five types of mechanoheat nociceptors (MHNs). Each of the MHN types is further categorized into two subtypes. Large DRG neurons are categorized into four types, including neurexophilin 1-expressing MHNs and mechanical nociceptors (MNs) expressing BAI1-associated protein 2-like 1 (Baiap2l1). Mechanoreceptors expressing trafficking protein particle complex 3-like and Baiap2l1-marked MNs are subdivided into two subtypes each. These results provide a new system for cataloging somatosensory neurons and their transcriptome databases.
Topics: Animals; Base Sequence; Cells, Cultured; Ganglia, Spinal; Gene Regulatory Networks; Male; Mechanoreceptors; Mice; Mice, Inbred C57BL; Multigene Family; Nociceptors; Patch-Clamp Techniques; Sensory Receptor Cells; Sequence Analysis, RNA; Transcriptome
PubMed: 26691752
DOI: 10.1038/cr.2015.149 -
Cell Nov 2022The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical...
The encoding of touch in the spinal cord dorsal horn (DH) and its influence on tactile representations in the brain are poorly understood. Using a range of mechanical stimuli applied to the skin, large-scale in vivo electrophysiological recordings, and genetic manipulations, here we show that neurons in the mouse spinal cord DH receive convergent inputs from both low- and high-threshold mechanoreceptor subtypes and exhibit one of six functionally distinct mechanical response profiles. Genetic disruption of DH feedforward or feedback inhibitory motifs, comprised of interneurons with distinct mechanical response profiles, revealed an extensively interconnected DH network that enables dynamic, flexible tuning of postsynaptic dorsal column (PSDC) output neurons and dictates how neurons in the primary somatosensory cortex respond to touch. Thus, mechanoreceptor subtype convergence and non-linear transformations at the earliest stage of the somatosensory hierarchy shape how touch of the skin is represented in the brain.
Topics: Animals; Mice; Spinal Cord Dorsal Horn; Mechanoreceptors; Touch; Interneurons; Brain; Spinal Cord
PubMed: 36334588
DOI: 10.1016/j.cell.2022.10.012 -
WormBook : the Online Review of C.... Jan 2006Wild C. elegans and other nematodes live in dirt and eat bacteria, relying on mechanoreceptor neurons (MRNs) to detect collisions with soil particles and other animals... (Review)
Review
Wild C. elegans and other nematodes live in dirt and eat bacteria, relying on mechanoreceptor neurons (MRNs) to detect collisions with soil particles and other animals as well as forces generated by their own movement. MRNs may also help animals detect bacterial food sources. Hermaphrodites and males have 22 putative MRNs; males have an additional 46 MRNs, most, if not all of which are needed for mating. This chapter reviews key aspects of C. elegans mechanosensation, including MRN anatomy, what is known about their contributions to behavior as well as the neural circuits linking MRNs to movement. Emerging models of the mechanisms used to convert mechanical energy into electrical signals are also discussed. Prospects for future research include expanding our understanding of the molecular basis of mechanotransduction and how activation of MRNs guides and modulates behavior.
Topics: Animals; Caenorhabditis; Caenorhabditis elegans; Mechanoreceptors; Mechanotransduction, Cellular; Neural Pathways
PubMed: 18050466
DOI: 10.1895/wormbook.1.62.1 -
The Journal of Physiology May 2022
Topics: Mechanoreceptors; Muscle Spindles; Proprioception; Vibration
PubMed: 35114007
DOI: 10.1113/JP282865 -
Physiology (Bethesda, Md.) May 2013The hairs of the skin not only function to prevent heat loss but also have important sensory functions. Recent work has now established that each hair of the skin is... (Review)
Review
The hairs of the skin not only function to prevent heat loss but also have important sensory functions. Recent work has now established that each hair of the skin is innervated by one or more of three types of mechanoreceptor ending. Each of these three mechanoreceptor types possesses distinct molecular features and detects distinctive information about skin touch, which is relayed to specific brain locations in a somatotopic fashion.
Topics: Afferent Pathways; Animals; Evoked Potentials; Hair; Hair Follicle; Humans; Mechanoreceptors; Mechanotransduction, Cellular; Neurons, Afferent; Skin; Touch
PubMed: 23636260
DOI: 10.1152/physiol.00059.2012 -
Nature Dec 2014The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that...
The sense of touch provides critical information about our physical environment by transforming mechanical energy into electrical signals. It is postulated that mechanically activated cation channels initiate touch sensation, but the identity of these molecules in mammals has been elusive. Piezo2 is a rapidly adapting, mechanically activated ion channel expressed in a subset of sensory neurons of the dorsal root ganglion and in cutaneous mechanoreceptors known as Merkel-cell-neurite complexes. It has been demonstrated that Merkel cells have a role in vertebrate mechanosensation using Piezo2, particularly in shaping the type of current sent by the innervating sensory neuron; however, major aspects of touch sensation remain intact without Merkel cell activity. Here we show that mice lacking Piezo2 in both adult sensory neurons and Merkel cells exhibit a profound loss of touch sensation. We precisely localize Piezo2 to the peripheral endings of a broad range of low-threshold mechanoreceptors that innervate both hairy and glabrous skin. Most rapidly adapting, mechanically activated currents in dorsal root ganglion neuronal cultures are absent in Piezo2 conditional knockout mice, and ex vivo skin nerve preparation studies show that the mechanosensitivity of low-threshold mechanoreceptors strongly depends on Piezo2. This cellular phenotype correlates with an unprecedented behavioural phenotype: an almost complete deficit in light-touch sensation in multiple behavioural assays, without affecting other somatosensory functions. Our results highlight that a single ion channel that displays rapidly adapting, mechanically activated currents in vitro is responsible for the mechanosensitivity of most low-threshold mechanoreceptor subtypes involved in innocuous touch sensation. Notably, we find that touch and pain sensation are separable, suggesting that as-yet-unknown mechanically activated ion channel(s) must account for noxious (painful) mechanosensation.
Topics: Animals; Ion Channels; Mechanoreceptors; Mechanotransduction, Cellular; Merkel Cells; Mice; Mice, Knockout; Sensory Receptor Cells; Skin; Touch
PubMed: 25471886
DOI: 10.1038/nature13980 -
Neuropharmacology Jul 2015It is well established that some members of the Deg/ENaC super family of amiloride sensitive ion channels can participate directly in the transduction of mechanical... (Review)
Review
It is well established that some members of the Deg/ENaC super family of amiloride sensitive ion channels can participate directly in the transduction of mechanical stimuli by sensory neurons in invertebrates. A large body of work has also implicated the acid sensing ion channels family (ASIC1-4) as participants in regulating mechanoreceptor sensitivity in vertebrates. In this review we provide an overview of the physiological and genetic evidence for involvement of ASICs in mechanosensory function. On balance, the available evidence favors the idea that these channels have an important regulatory role in mechanosensory function. It is striking how diverse the consequences of Asic gene deletion are on mechanosensory function with both gain and loss of function effects being observed depending on sensory neuron type. We conclude that other, as yet unknown, molecular partners of ASIC proteins may be decisive in determining their precise physiological role in mechanosensory neurons. This article is part of the Special Issue entitled 'Acid-Sensing Ion Channels in the Nervous System'.
Topics: Acid Sensing Ion Channels; Animals; Humans; Mechanoreceptors
PubMed: 25528740
DOI: 10.1016/j.neuropharm.2014.12.007 -
Developmental Cell Oct 2023Mechanosensory neurons innervating the skin underlie our sense of touch. Fast-conducting, rapidly adapting mechanoreceptors innervating glabrous (non-hairy) skin form...
Mechanosensory neurons innervating the skin underlie our sense of touch. Fast-conducting, rapidly adapting mechanoreceptors innervating glabrous (non-hairy) skin form Meissner corpuscles, while in hairy skin, they associate with hair follicles, forming longitudinal lanceolate endings. How mechanoreceptors develop axonal endings appropriate for their skin targets is unknown. We report that mechanoreceptor morphologies across different skin regions are indistinguishable during early development but diverge post-natally, in parallel with skin maturation. Neurons terminating along the glabrous and hairy skin border exhibit hybrid morphologies, forming both Meissner corpuscles and lanceolate endings. Additionally, molecular profiles of neonatal glabrous and hairy skin-innervating neurons largely overlap. In mouse mutants with ectopic glabrous skin, mechanosensory neurons form end-organs appropriate for the altered skin type. Finally, BMP5 and BMP7 are enriched in glabrous skin, and signaling through type I bone morphogenetic protein (BMP) receptors in neurons is critical for Meissner corpuscle morphology. Thus, mechanoreceptor morphogenesis is flexibly instructed by target tissues.
Topics: Mice; Animals; Mechanoreceptors; Neurons; Skin; Touch; Hair
PubMed: 37607547
DOI: 10.1016/j.devcel.2023.07.020